Targeting the small airways with dry powder adenosine: a challenging concept

摘要

Background: Small-particle inhaled corticosteroids (ICS) provide a higher small airway deposition than large-particle ICS. However, we are still not able to identify asthma patients who will profit most from small-particle treatment.Objective: We aimed to identify these patients by selectively challenging the small and large airways. We hypothesized that the airways could be challenged selectively using small- and large-particle adenosine, both inhaled at a high and a low flow rate.Design: In this cross-over study 11 asthma subjects performed four dry powder adenosine tests, with either small (MMAD 2.7?μm) or large (MMAD 6.0?μm) particles, inhaled once with a low flow rate (30?l?min~(–1)) and once with a high flow rate (60?l?min~(–1)). Spirometry and impulse oscillometry were performed after every bronchoprovocation step. We assumed that FEV_(1) reflects the large airways, and FEF_(25–75%), R5-R20 and X5 reflect the small airways.Results: The four adenosine tests were not significantly different with respect to the threshold values of FEV_(1) (p ?=?0.12), FEF_(25–75%) (p ?=?0.37), R5-R20 (p ?=?0.60) or X5 (p ?=?0.46). Both small- and large-particle adenosine induced a response in the small airways in the majority of the tests.Conclusions: In contrast to our hypothesis, all four adenosine tests provoked a response in the small airways and we could not identify different large- or small-airway responders. Interestingly, even the test with large particles and a high flow rate induced a small-airway response, suggesting that selective challenging of the small airways is not necessary. Future studies should investigate the relation between particle deposition and the site of an airway response.